Genes, Gene Expression + DNA Biology

Human health and disease can both be traced to the actions of the genetic information encoded within our DNA. Wistar researchers are at the forefront of the basic biological research that resides at the heart of modern, scientific medicine.

Genes, Gene Expression + DNA Biology

The field of bioinformatics applies computer science and information technology to complex problems in the study of biological processes, such as the network of interactions between molecules within cells or the analysis of mutations in cancer.

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Chromatin is the “packaged” form of DNA in the nucleus and its regulation is central to transcription – creating the RNA copy of a DNA sequence. Chromatin helps assure that the DNA/RNA copy is precise – any deviation can result in stunted gene expression or proteins that no longer function properly. Chromatin dysregulation has been implicated in diseases ranging from immune diseases and neurological disorders to cancers.

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Computational genomics uses the power of computing, mathematics and statistics to study the genome, particularly DNA and RNA sequencing. Because deciphering the genome and gene function is essential to understanding basic biology at the molecular level, this analytical, data driven approach can help identify new targets for therapeutic and vaccine development.

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Broadly defined, epigenetics is the study of hereditary changes in gene activity without changes in the genome or genetic code itself. These changes can be caused by environmental influences such as exposure to toxins, viral infections, and even diet. These influences work by altering the activation of certain genes, and the changes are passed on during cell division.

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Experimental therapeutics is the science of turning the basic processes and mechanisms of human biology into new, more effective drugs and medical devices. One goal is to create more “personalized” therapeutics to better fit the biology of individual patients with higher efficacy, more specificity, and lower side effects.

Gene expression is how information encoded within DNA becomes an active molecule, particularly a protein. The process is regulated at several points, and any disturbance in the pathway can result in the onset of a number of diseases, including cancer. Research into gene regulation is focused on determining how variations in DNA and gene expression result in disease, and uncovering the molecular mechanisms that control them.

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The new wealth of information about the human genome has led to a surge in the role of functional genomics, which seeks to uncover the function of newly discovered genes and their expressed proteins. Functional genomics explores the dynamic processes that regulate both genes and proteins.

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Kinase signaling is a process that helps coordinate and amplify communications between cells; kinases are enzymes that add a phosphate group to macromolecules and alter their actions. While protein kinases are the largest group, other types of kinases work with carbohydrates, lipids and amino acids. Therapeutics that inhibit kinases are often used in cancer treatment.

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Determining the structure of proteins is the first step towards understanding their function. Wistar Institute researchers are currently working to create 3D molecular models of proteins, as well as detailed analyses of structural properties such as protein-ligand docking and protein-protein interaction.

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There are approximately 35,000 genes in the human genome that provide the code for at least ten times as many proteins. Proteomics seeks to identify and analyze the structure, function, and interactions of these tens of thousands of proteins expressed by our genes. Understanding how they work in the cell is essential to a greater understanding of virtually all biological processes.

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RNA (ribonucleic acid) biology is the study of the function and structure of this important molecule, which is critical to gene expression and protein synthesis. Because RNA is at the heart of gene expression, it touches virtually all human genetic diseases, and plays a key role in gene regulation – approximately one-tenth of the human genome belongs to regulatory RNA.

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Signal transduction is the transfer of signals from outside the cell to the inside, which creates a cellular response. These signals are carried by receptors that span both sides of the cell membrane; an outside molecule binds to the receptor, alters its shape and sends a signal to the cell’s interior. Ultimately, this may result in changes to gene expression or the activity of various cellular enzymes.

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The related fields of systems and integrative biology seek to understand the wide range of biologically complex processes in an organism as well as the mechanisms underlying those processes. This approach to biology involves a number of scientific disciplines from biochemistry to cell biology–on a scale that can range from the molecular, cellular or tissue level to entire systems within the organism itself.

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Telomeres, bits of repetitive DNA sequences on the tips of chromosomes, are important for maintaining the stability and integrity of our genetic code. During normal cell division, telomeres are shortened. In humans, this shortening process as well as the activation of an enzyme called telomerase has been closely linked to cancer and aging.